Literature DB >> 10228161

Impaired neutral sphingomyelinase activation and cutaneous barrier repair in FAN-deficient mice.

D Kreder1, O Krut, S Adam-Klages, K Wiegmann, G Scherer, T Plitz, J M Jensen, E Proksch, J Steinmann, K Pfeffer, M Krönke.   

Abstract

The WD-40 repeat protein FAN binds to a distinct domain of the p55 receptor for tumor necrosis factor (TNF) and signals the activation of neutral sphingomyelinase (N-SMase). To analyze the physiological role of FAN in vivo, we generated FAN-deficient mice by targeted gene disruption. Mice lacking a functional FAN protein do not show any overt phenotypic abnormalities; in particular, the architecture and cellular composition of lymphoid organs appeared to be unaltered. An essential role of FAN in the TNF-induced activation of N-SMase was demonstrated using thymocytes from FAN knockout mice. Activation of extracellular signal-regulated kinases in response to TNF treatment, however, was not impaired by the absence of the FAN protein. FAN-deficient mice show delayed kinetics of recovery after cutaneous barrier disruption suggesting a physiological role of FAN in epidermal barrier repair. Although FAN exhibits striking structural homologies with the CHS/Beige proteins, FAN-deficient mice did not reproduce the phenotype of beige mice.

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Year:  1999        PMID： 10228161      PMCID： PMC1171329          DOI： 10.1093/emboj/18.9.2472

Source DB:  PubMed          Journal:  EMBO J        ISSN： 0261-4189            Impact factor:   11.598


  26 in total

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  18 in total

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Review 7.  Stress test of the skin: The cutaneous permeability barrier treadmill.

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